Angiotensin II, Independent of Plasma Renin Activity, Contributes to the Hypertension of Autonomic Failure

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2013-03, Vol.61 (3), p.701-706
• Main Authors: Arnold, Amy C, Okamoto, Luis E, Gamboa, Alfredo, Shibao, Cyndya, Raj, Satish R, Robertson, David, Biaggioni, Italo
• Format: Article
• Language: English
• Subjects: Aged; Aldosterone - blood; Angiotensin II - blood; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Antihypertensive Agents - therapeutic use; Captopril - therapeutic use; Double-Blind Method; Female; Humans; Hypertension - blood; Hypertension - drug therapy; Losartan - therapeutic use; Male; Middle Aged; Orthostatic Intolerance - blood; Orthostatic Intolerance - drug therapy; Pure Autonomic Failure - blood; Pure Autonomic Failure - drug therapy; Renin - blood; Sodium - metabolism
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.111.00377

At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. Although the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable, suggesting renin–angiotensin (Ang) pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that Ang II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating Ang II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/mL, n=11) compared with matched healthy controls (27±4 pg/mL, n=10; P=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/mL per hour, respectively; P=0.449). To determine the contribution of Ang II to supine hypertension in these patients, we administered the AT1 receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mm Hg at 6 hours after administration (P